Comparative structure–activity relationships of green-synthesized silver, zinc oxide, and selenium nanoparticles mediated by Peganum harmala: physicochemical characteristics and multifunctional biological activities

Abstract

Background An environmentally responsible route to sustainable nanomaterial production is provided by green synthesis, enabling multifunctional bioactive systems intended for potential biomedical applications. Plant-mediated processes can reduce cost and environmental burden relative to conventional nanoparticle fabrication methods; phytochemical surface capping may also strengthen biological functionality in the resulting materials. In this study, Peganum harmala L. seed extract, a medicinal plant rich in flavonoids, phenolics, and terpenoids, was used as the plant source for biosynthesis. Methods Silver nanoparticles (Ag-NPs), zinc oxide nanoparticles (ZnO-NPs), and selenium nanoparticles (Se-NPs) were synthesized using Peganum harmala extract as a natural reducing and stabilizing agent. The synthesized nanoparticles were characterized by UV–visible spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. Their biological activities were evaluated through a series of in vitro assays, including antioxidant capacity (total antioxidant capacity, reducing power, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), and nitric oxide scavenging (NO), carbohydrate-metabolizing enzyme (α-amylase, α-glucosidase, and aldose reductase), Results The three nanoparticle systems exhibited distinct, pathway-specific biological activities consistent with their physicochemical profiles. ZnO-NPs (PDI = 0.184; zeta = +23.1 mV) demonstrated superior antioxidant and anti-diabetic enzyme inhibitory activities, with the lowest IC₅₀ values across DPPH, ABTS, α-amylase, α-glucosidase, and aldose reductase assays. Se-NPs (PDI = 0.091; zeta = +19.8 mV) exhibited the strongest anti-inflammatory (cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) and anti-arthritic activities, with IC₅₀ values approaching those of standard drugs. All three nanoparticles showed moderate, comparable cholinesterase inhibition. Ag-NPs consistently showed the weakest performance across most pathways, potentially related to their lower zeta potential (−14.4 mV) and reliance on steric rather than electrostatic stabilization. Conclusions The synthesized nanoparticles exhibited distinct bio functional profiles governed by elemental composition and physicochemical characteristics. ZnO-NPs were predominantly associated with antioxidant and anti-diabetic activities, whereas Se-NPs demonstrated superior anti-inflammatory and anti-arthritic properties. These findings highlight P. harmala-mediated nanoparticle synthesis as a sustainable and versatile platform for developing multifunctional nanomaterials with promising biomedical applications.